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LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.

The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a challenge. Rituximab-based strategies may be improved by adding chemotherapy. This Lymphoma Study Association multicentre phase II study assessed rituximab and bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old and had a follicular lymphoma International Prognostic Index (FLIPI) score ≥2. Induction comprised 4 weekly cycles of rituximab 375 mg/m intravenously combined with 2 cycles of bendamustine 90 mg/m days 1-2 with a 28-day interval, followed by twelve cycles of 375 mg/m rituximab maintenance therapy every 8 weeks. The primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks. Median age was 67·4 years and median FLIPI was 3. Ultimately, 18 patients (29%) had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires criteria. The 12-week CR/CRu rate was 54·0% and the overall response rate was 93·7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm). Progression-free survival was 85·4% at 24 months. In LTBFL patients with FLIPI ≥2, two cycles of rituximab and bendamustine result in a CR rate of 54·0%. However, the treatment-related deaths observed do not allow this regimen to be recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14; ClinicalTrials.gov: NCT01313611.

Teacher questioning in mathematics is an important diagnostic tool for teaching as well as measuring the academic progression and comprehension of the learner. While teacher questioning enhances student learning and self-assessment of the teacher’s lesson delivery effectiveness, if not presented properly can have negative impacts on the student learning process. Identifying “good” and/or “effective” questioning strategies is a major challenge to mathematics teachers. To increase teacher effectiveness and student success in mathematics, a self-assessment of teacher questioning techniques is essential. This study examines the questioning strategies used by two grade 8 teachers, selected at random, from twelve middle school teachers each handling quadratic mathematical modeling as one of their lessons in a project. The purpose of this study was to determine the questioning strategies used by the two teachers in their mathematical classroom discourse. Each class was videotaped over six-month period but only a section from each of the two selected classes, on quadratic modeling, was watched for about 45 minutes long for the purpose of this paper. A common theme “teacher questioning strategies” was the bases for analyzing the data. The strategies include: probing and follow-up, leading, check-listing and student-specific questioning. Findings from the study indicate that guiding teachers (pre-service and in-service) through an analysis of questions they ask and the responses they get from students during mathematical discourse, may enable them recognize both effective and ineffective questioning strategies in their mathematical classroom discourse. This study may help both pre-service and in-service teachers as well as teacher-researchers to be well aware of their questioning practices by reflecting on the questioning strategies they use in their own mathematical classroom discourse. Keywords: probing and follow-up, scaffolding, checklisting strategy, leading questions, s

Teacher questioning in mathematics is an important diagnostic tool for teaching as well as measuring the academic progression and comprehension of the learner. While teacher questioning enhances student learning and self-assessment of the teacher’s lesson delivery effectiveness, if not presented properly can have negative impacts on the student learning process. Identifying “good” and/or “effective” questioning strategies is a major challenge to mathematics teachers. To increase teacher effectiveness and student success in mathematics, a self-assessment of teacher questioning techniques is essential. This study examines the questioning strategies used by two grade 8 teachers, selected at random, from twelve middle school teachers each handling quadratic mathematical modeling as one of their lessons in a project. The purpose of this study was to determine the questioning strategies used by the two teachers in their mathematical classroom discourse. Each class was videotaped over six-month period but only a section from each of the two selected classes, on quadratic modeling, was watched for about 45 minutes long for the purpose of this paper. A common theme “teacher questioning strategies” was the bases for analyzing the data. The strategies include: probing and follow-up, leading, check-listing and student-specific questioning. Findings from the study indicate that guiding teachers (pre-service and in-service) through an analysis of questions they ask and the responses they get from students during mathematical discourse, may enable them recognize both effective and ineffective questioning strategies in their mathematical classroom discourse. This study may help both pre-service and in-service teachers as well as teacher-researchers to be well aware of their questioning practices by reflecting on the questioning strategies they use in their own mathematical classroom discourse. Keywords: probing and follow-up, scaffolding, checklisting strategy, leading questions, s

Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

This paper aims at contributing to the body of knowledge that exists in the area of differences in participation in elective mathematics, between boys and girls in Secondary Schools in Ghana. A sample of 738 respondents from five Secondary Schools was purposively selected using purposive sampling technique. All the respondents were final year students and had studied extensively more than a half of the elective mathematics syllabus. The selected schools were made up of two single-sex female schools, one single-sex male school and one mixed-sex schools from Cape Coast municipality in the central region and one mixed-sex school, from Sekondi in the western region of Ghana. Relevant data were gathered using a set of questionnaire and an interview schedule prepared by the researchers. The analysis of the personal interviews with some of the female respondents revealed various reasons why some females were attracted to the study of elective mathematics. The study revealed that the participation of males in elective mathematics was 50.5% while that of females was 27.2% giving an indication that females participated in elective mathematics less often than their male counterparts. Suggestions for increasing female participation in senior secondary school elective mathematics were made and areas for further research on the topic have also been suggested. Keywords: Senior Secondary School, Participation, STME Clinics, Mixed Sex Male, Mixed Sex Female, Single Sex- Female, Single Sex-Male.

Educational authorities in Ghana have generally established that the performance of school leavers especially at the pre-university level offered a large room for improvement, due to so many factors. Hence, the introduction of the New Educational Reform in 1987 which led to the new system of Senior Secondary School with the first product in 1993. The study was to create awareness of whether Ghana’s New Educational Reform, which has been in place since 1987, has led to improvement in performance of Senior Secondary Schools in Ghana in the area of the four core disciplines: Mathematics, Integrated Sciences, Social Studies, and English language. Two–way Analysis of Variance (ANOVA) without replication was derived to determine whether significant differences existed between grades, subjects and the years involved in the study to obtain some dimensions for determining the performance of students in the institution. Social Studies and the grades C, D and E gave the institution a glorious image while Mathematics, Integrated Science and English Language and grade F, gave the institution a poor image. However, majority of the grades A and B were associated with Core Mathematics. There was no significant difference in the trend of students’ performance between years in the study period. We recommend that future research spanning a period from 2006 to 2014, which has different grading system, under the West African Senior School Certificate Examination (WASSCE) grading system, be done in a comparative manner. This might include students in two or three regions of Ghana. To make the research generalizable, random samples of schools and students must be considered. Keywords: Percentage number of grades; interaction; replications; West African Senior School Certificate Examination (WASSCE) grading system.

This paper aims at contributing to the body of knowledge that exists in the area of differences in participation in elective mathematics, between boys and girls in Secondary Schools in Ghana. A sample of 738 respondents from five Secondary Schools was purposively selected using purposive sampling technique. All the respondents were final year students and had studied extensively more than a half of the elective mathematics syllabus. The selected schools were made up of two single-sex female schools, one single-sex male school and one mixed-sex schools from Cape Coast municipality in the central region and one mixed-sex school, from Sekondi in the western region of Ghana. Relevant data were gathered using a set of questionnaire and an interview schedule prepared by the researchers. The analysis of the personal interviews with some of the female respondents revealed various reasons why some females were attracted to the study of elective mathematics. The study revealed that the participation of males in elective mathematics was 50.5% while that of females was 27.2% giving an indication that females participated in elective mathematics less often than their male counterparts. Suggestions for increasing female participation in senior secondary school elective mathematics were made and areas for further research on the topic have also been suggested. Keywords: Senior Secondary School, Participation, STME Clinics, Mixed Sex Male, Mixed Sex Female, Single Sex- Female, Single Sex-Male.

Educational authorities in Ghana have generally established that the performance of school leavers especially at the pre-university level offered a large room for improvement, due to so many factors. Hence, the introduction of the New Educational Reform in 1987 which led to the new system of Senior Secondary School with the first product in 1993. The study was to create awareness of whether Ghana’s New Educational Reform, which has been in place since 1987, has led to improvement in performance of Senior Secondary Schools in Ghana in the area of the four core disciplines: Mathematics, Integrated Sciences, Social Studies, and English language. Two–way Analysis of Variance (ANOVA) without replication was derived to determine whether significant differences existed between grades, subjects and the years involved in the study to obtain some dimensions for determining the performance of students in the institution. Social Studies and the grades C, D and E gave the institution a glorious image while Mathematics, Integrated Science and English Language and grade F, gave the institution a poor image. However, majority of the grades A and B were associated with Core Mathematics. There was no significant difference in the trend of students’ performance between years in the study period. We recommend that future research spanning a period from 2006 to 2014, which has different grading system, under the West African Senior School Certificate Examination (WASSCE) grading system, be done in a comparative manner. This might include students in two or three regions of Ghana. To make the research generalizable, random samples of schools and students must be considered. Keywords: Percentage number of grades; interaction; replications; West African Senior School Certificate Examination (WASSCE) grading system.

The purpose of the study was to determine the main causes of students’ misbehaviour and measures teachers and students consider to be most appropriate for controlling the unruly behaviour of the students. Purposive, sample, of 50 teachers who held the various positions in the school, and 150 students comprising the Students Representative Council, the class prefects and the class secretaries, was used for the study. Descriptive sample survey was considered to be most appropriate method for the study. A questionnaire was used to collect data from the participants. Majority of the respondents shared the opinion that it is the students themselves who cause such acts of indiscipline. It is only with students late to school and demonstrations that the majority of the respondents attributed the causes to parents and school respectively. A careful look at the statistics of causes of acts of indiscipline on Table 1 shows that apart from the individuals themselves, the school is the next cause of most of the acts of indiscipline. The community closely follows with parents and the media being almost at par. With regard to the measures of ensuring discipline in the School, all the ten measures that were listed were considered by at least 90% of the respondents to be very important. Keywords: students’ misbehaviour, Students Representative Council, and descriptive survey.

Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (Clin